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p21: prognostic marker in pleural mesothelioma

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Mesothelioma stained with monoclonal antibody to p21. (A) Mixed mesothelioma with ≤10% of positive cells; (B) sarcomatoid mesothelioma with >10% positive cells. Original magnification ×400.

Expression of p21—an inhibitor of the cell cycle—may hold an important clue to events leading to malignant mesothelioma. Normally p21 expression is upregulated by the binding of p53 to the p21 promoter, but in malignant mesothelioma—an important cancer of the pleura—it may be silenced by the binding and inactivation of p53 by simian virus 40 large T antigen (SV40Tag). This preliminary study supports the hypothysis.

Expression of p21 in specimens of malignant mesothelioma was not significantly related to histological type in the study. However, median survival in the patients was significantly greater for specimens expressing p21 in more than 10% of cells (median difference in survival 7 months, 95% confidence interval 4.8 to 9.9 months), and Kaplan-Meier analysis confirmed the relation.

Twenty nine specimens of malignant mesothelioma were assessed—all known to be positive for SV40Tag. Sixteen tumours were epithelial, six sarcomatoid, and seven were mixed tumours. p21 expression was determined with a specially developed immunohistochemical method capable of discriminating non-cancerous cell types (stroma and endothelial and inflammatory cells). Survival data were obtained from patients’ notes or interviews with relatives and excluded two deaths from causes unrelated to mesothelioma.

Malignant mesothelioma is increasing. It is not always caused by asbestos, and the exact mechanism of pathogenesis is unknown, though recently SV40Tag has been implicated through binding to p53. As a downstream target of p53, p21 is a potential candidate for studying the molecular mechanisms of pathogenesis.